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ArtículoDerechos de autor
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Fecha del embargo
2022-01-01
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- IOC - Artigos de Periódicos [12500]
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ACTIVATION OF TRANSFORMING GROWTH FACTOR BETA BY TRYPANOSOMA CRUZI
Transformando o fator de crescimento b
Ativação
TGFbeta
Afiliación
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Unité INSERM EMI 105. Department of Cellular Responses and Dynamics. Grenoble, France.
Resumen en ingles
The anti-inflammatory cytokine, transforming growth factor beta (TGFbeta), plays an important role in Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi. In the current study, we show that the addition of an anti-TGFbeta antibody inhibited T. cruzi infection of cardiomyocytes, demonstrating the requirement for active endogenous TGFbeta. As TGFbeta is synthesized as a biologically inactive precursor, which is proteolytically processed to yield a mature, active homodimer, we hypothesized that T. cruzi could activate latent TGFbeta. To test this, we added recombinant latent TGFbeta to a TGFbeta-responsive reporter cell line in the presence of T. cruzi. We observed that T. cruzi was able to activate latent recombinant TGFbeta in this cellular model. We then investigated the ability of T. cruzi to activate latent TGFbetain vitro. We found that live T. cruzi, or cytosolic extracts of T. cruzi, activated latent TGFbeta in a dose- and temperature-dependent manner. The agent involved in TGFbeta activation was shown to be thermolabile and hydrophobic. Taken together, our studies demonstrate that T. cruzi directly activates latent TGFbeta. This activation is required for parasite entry into the mammalian cells and is likely to play an important role in modulating the outcome of T. cruzi infection.
Palabras clave en portugues
Trypanosoma cruziTransformando o fator de crescimento b
Ativação
TGFbeta
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